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Structure of the Potato Inhibitor Complex of Carboxypeptidase A at 2.5Å Resolution

Rees, Douglas C. and Lipscomb, William N. (1980) Structure of the Potato Inhibitor Complex of Carboxypeptidase A at 2.5Å Resolution. Proceedings of the National Academy of Sciences of the United States of America, 77 (8). pp. 4633-4637. ISSN 0027-8424. PMCID PMC349899. https://resolver.caltech.edu/CaltechAUTHORS:20150210-100406855

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Abstract

The structure of the complex between the proteolytic enzyme carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and the 39-amino-acid carboxypeptidase A inhibitor from potatoes has been determined at 2.5-Å resolution. A combination of multiple isomorphous replacement, molecular replacement, and noncrystallographic symmetry averaging techniques was used to solve the structure. The chain trace of the inhibitor and details of the binding interactions in the complex are described. A surprising aspect of the complex is that the carboxy-terminal peptide bond of the inhibitor has been hydrolyzed, and the carboxy-terminal glycine is trapped in the binding pocket of carboxypeptidase A. Consequently, the complex resembles a stage in the catalytic mechanism after hydrolysis of the peptide bond. The ring of tyrosine-248, which is known to undergo large conformational changes upon substrate binding, is in the "down" position and interacts with the inhibitor in the complex.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.pnas.org/content/77/8/4633PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349899/PubMed CentralArticle
ORCID:
AuthorORCID
Rees, Douglas C.0000-0003-4073-1185
Additional Information:© 1980 National Academy of Sciences. Contributed by William N. Lipscomb, May 16, 1980. We thank the National Institutes of Health (Grant GM 06920) for support of this research. W.N.L. also thanks the Alexander von Humboldt Foundation for an award that aided this research. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S. C. §1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHGM 06920
Alexander von Humboldt FoundationUNSPECIFIED
Subject Keywords:enzyme complex; protease inhibitor; protein crystallography
Issue or Number:8
PubMed Central ID:PMC349899
Record Number:CaltechAUTHORS:20150210-100406855
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150210-100406855
Official Citation:D C Rees and W N Lipscomb Structure of the potato inhibitor complex of carboxypeptidase A at 2.5-A resolution PNAS 1980 77 (8) 4633-4637
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54655
Collection:CaltechAUTHORS
Deposited By: SWORD User
Deposited On:11 Feb 2015 00:02
Last Modified:03 Oct 2019 07:59

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